Pharmacology: Clearance and Elimination

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Questions and Answers

What is the unit of measurement for clearance?

mg/L

L/hr or ml/min (correct)

mg/hr

mg/mL

What determines the rate of elimination of a drug?

The plasma concentration of the drug (correct)

The patient's age

The patient's weight

The dose of the drug administered

What is the total body clearance (CL total) of a drug?

The sum of all clearances from the drug-eliminating organs

The sum of all clearances from the drug-metabolizing and drug-eliminating organs (correct)

The difference between the liver and kidney clearance

The sum of all clearances from the drug-metabolizing organs

What is the effect of a high plasma concentration on the rate of elimination?

It increases the rate of elimination Signup and view all the answers

What is the equation for calculating total clearance?

CL = CL hepatic + CL renal Signup and view all the answers

Which organ is the major contributor to drug excretion?

Kidney Signup and view all the answers

What is the formula to calculate Clearance (CL)?

CL = Q × (Ci - Co) Signup and view all the answers

What is the purpose of determining the Elimination Half-life (t1/2) of a drug?

To determine the duration of action of a drug Signup and view all the answers

How does an increase in Volume of distribution (Vd) affect the Elimination Half-life (t1/2) of a drug?

It increases t1/2 Signup and view all the answers

What is the effect of Renal failure on the Elimination Half-life (t1/2) of a drug?

It increases t1/2 Signup and view all the answers

How does an increase in Clearance (CL) affect the Elimination Half-life (t1/2) of a drug?

It decreases t1/2 Signup and view all the answers

What is the effect of CYP450 induction on the Elimination Half-life (t1/2) of a drug?

It decreases t1/2 Signup and view all the answers

What is the renal clearance of a drug calculated as?

The rate of renal excretion divided by the plasma drug concentration Signup and view all the answers

What is the glomerular filtration rate (GFR) measured as?

The volume of blood filtered through the glomerular capillaries per unit of time Signup and view all the answers

Why is creatinine used to measure glomerular filtration rate (GFR)?

Because it is freely filtered by the glomerulus Signup and view all the answers

What does a high hepatic extraction ratio indicate?

A large first-pass effect Signup and view all the answers

What is the hepatic extraction ratio calculated as?

Q × (Ci – Co) Signup and view all the answers

What does a renal clearance higher than creatinine clearance indicate about a drug?

That it undergoes tubular secretion Signup and view all the answers

Study Notes

Clearance (CL)

Defined as the volume of plasma cleared from the drug per unit time (L/hr or ml/min)
Total body clearance (CL total) is the sum of all clearances from drug-metabolizing and drug-eliminating organs
Kidney is the major organ of excretion, liver also contributes to drug clearance through metabolism and/or excretion into the bile

Factors Affecting Clearance

Clearance depends on plasma concentration: high concentration → high rate of elimination, low concentration → low rate of elimination
Clearance equation: CL = Q × (Ci – Co)

Elimination Half-life (t1/2)

Time required for plasma concentration of a drug to decrease by 50%
Depends on Vd and CL: t1/2 α Vd, t1/2 α 1/CL
Used to determine duration of action and frequency of dosing

Factors Affecting Half-life

Volume of distribution (Vd): ↑Vd → ↑t1/2, ↓Vd → ↓t1/2
Clearance (CL): ↑CL → ↓t1/2, ↓CL → ↑t1/2
Aging: ↓Vd → ↓t1/2
Obesity: ↑Vd → ↑t1/2
Pathologic fluids: ↑Vd → ↑t1/2
CYP450 induction: ↓t1/2
CYP450 inhibition: ↑t1/2
Cardiac failure: ↓tissue perfusion → ↓clearance → ↑t1/2
Hepatic failure: ↓clearance → ↑t1/2
Renal failure: ↓clearance → ↑t1/2

Renal Clearance

Renal excretion rate divided by plasma drug concentration
Calculated using glomerular filtration rate (GFR) which can be measured using creatinine clearance rate (CrCl)

Extraction Ratio

Removal of a drug by an organ specified as the extraction ratio
Hepatic extraction ratio: fraction or percentage of the drug removed from the perfusing blood during its passage through the liver
Drugs with high hepatic extraction ratio: large first-pass effect, low oral bioavailability

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Description

This quiz covers the concept of clearance in pharmacology, including total body clearance, its calculation, and the role of organs like the kidney and liver in drug clearance.